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BackTable / Urology / Article
Tools for Prostate Cancer Screening & Risk Stratification
Lauren Fang • Apr 6, 2024 • 38 hits
Prostate cancer screening tools, such as the multiparametric MRI and molecular testing techniques, allow for enhanced patient selection for prostate biopsies, while guiding prostate cancer risk stratification. The multiparametric MRI is employed prior to the use of a more invasive biopsy procedure in order to visualize clinically significant prostate cancers. Similarly, urologist Ali Kasraeian utilizes molecular testing for various biomarkers in tandem with PSA blood tests and MRI scans that are found to be ambiguous, as a means of solidifying the recommendation for or against active patient surveillance.
This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable Urology Brief
•Dr. Kasraeian uses PSA trajectory and multiparametric MRI scan as a means of determining which patients should undergo prostate biopsies. Biomarker testing, such as ExosomeDx, is employed when the PSA velocity and/or MRI scan are equivocal.
•Multiparametric MRI of the prostate offers visualization of potentially clinically significant prostate cancers. It is a valuable tool for selecting patients for biopsy, monitoring patients under active surveillance, staging tumors, and analyzing treatment responses.
•Genomic profiling is available through commercial molecular biomarker tests such as Prolaris, Decipher, and Oncotype Dx and help to categorize patients as low or high risk of prostate cancer, further aiding physicians in their decision to assign patients to surveillance or treatment.
Table of Contents
(1) Multiparametric MRI to Guide Prostate Cancer Screening
(2) Biomarkers & Molecular Testing for Prostate Risk Stratification
Multiparametric MRI to Guide Prostate Cancer Screening
Multiparametric MRI is a valuable tool to add to a physician’s prostate cancer screening plan, posits Dr. Kasraeian, given its use in deciphering which patients are candidates for biopsy. Prostate MRI is indicated when a negative transrectal ultrasound is observed, and it aids in detecting occult prostate cancer in cases where patients exhibit continuously elevated PSA levels and a negative transrectal ultrasound biopsy. With the currently available technology, prostate MRI scans alone do not provide enough information to proceed straight to treatment without the use of a biopsy in conjunction, however, the screening technique does both facilitate lesion targeting and improve patient selection for more invasive procedures.
[Dr. Jose Silva]
…How do you integrate MRI? Are you doing MRI on everybody that has a PSA or what are you doing first?
[Dr. Ali Kasraeian]
To answer your question, we try to get MRI scans on everyone that we're going to do a biopsy for the power of both the negative MRI scan but also the positive MRI scan.
Not only does it set us up for the possibility of having a negative MRI scan to help us make a decision in terms of biopsy or no biopsy and a standard biopsy versus a targeted biopsy, but in terms of future follow-up or people on active surveillance. It may potentially help guide us in terms of delaying the time in between biopsies. We can use this information in combination with biomarkers, things like ExosomeDX, the 4K score.
We've done multicenter trials with different groups in looking at not only the validity or value of this process but also the ultimate question that I don't think anyone has an answer to, which one do you do first? Do you do the biomarker first? Do you do the MRI scan first? I don't think anyone has an answer. It depends on the patient and the scenario.
[Dr. Jose Silva]
Do you think it's going to be the time at some point that we go to treat prostate cancer without actually doing a biopsy, just based on MRI? For some reason, I'm seeing more patients that are afraid of just the biopsy. They're not afraid of cancer, of getting a radical prostatectomy, they just don't want the biopsy, what do you think?
[Dr. Ali Kasraeian]
Well, it's interesting. There's some papers coming out of people going to prostatectomy straight from MRI scan. I know I wouldn't do that. I'd be a little bit terrified of having an MRI scan and coming out with a negative prostatectomy. I don't know how happy anyone would be with that result and I don't know how that conversation goes and post-prostatectomy discussion, but where that will mature to, it'll take some time.
…For the multiparametric MRI scan, I know I've been looking at them. In the next year or two, it'll be a decade, and so I feel comfortable looking at them, but I still talk to my radiologist every time I look at one and we confer and discuss it and make sure that we're both on the same page from that standpoint.
That's something that is worthwhile for my patient but I only have the same two people that have been reading my MRI scan since we started. That's important for the patients because there's consistency. Some places that's not the case. However, if you had everyone that read it the same way, it was something that was just part of reading radiology images that would be a little bit more of a thing that we could potentially think about .
The other problem that we have with prostate cancer is the grading system and the differences in how we manage different Gleason scores. Gleason 6 prostate cancer in one or two cores is different from the Gleason 9 or 10 prostate cancer involving the whole prostate. Unless the MRI scan can give us some absolutes in that information, it'd be very difficult for us to avoid the biopsy because of the profound amount of information we gather from what the imaging tells us.
Technology has to be able to give us some grading information beyond PI-RADS 4 and 5, PI-RADS 3, 1 and 2 because right now PI-RADS 4 and 5 tell us that the risk of cancer that's Gleason seven or higher is increased. PI-RADS 4, we have a higher suspicion that it's going to be cancer. All of us have done biopsies where a PI-RADS 4 lesion sometimes is a 4+3=7, sometimes it's an 8, but it's not as exact as you see a Gleason score and you act on it from that standpoint.
Once that gets better, once we can get more information that we can act upon, then we can potentially go to treatment straight off the MRI scan without the biopsy because what we do and the spectrum of treatment is a bit different. Right now, that may change.
…The earlier we find cancer the better. Right now, the big conversation is we don't want to find low-volume Gleason 6 cancer, as weird as that sound. The MRI scan was not designed to find one core of Gleason 6 cancer. Most people agree that it is not a fatal disease. The idea is how do we use these tools to find the disease that matters? The Europeans say if the MRI is negative, do we need to do a biopsy?
The US side has not gotten to that point yet. In the active surveillance protocols, we still talk about doing biopsies in a regimented manner. I remember when I was shadowing European clinics in London, the MRI scan drove what to do next. An important part of that discussion is our confidence in our radiologists and ourselves in reading the MRI scans to be confident we're not missing anything. I don't think nationally we're quite there yet. Hopefully, we will continue to get there. It's important for urologists to learn how to read the MRI scans well for us to get there.
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Biomarkers & Molecular Testing for Prostate Risk Stratification
Molecular tests, such as Exosome Diagnostics (ExoDx), assist in managing the treatment of patients with low to intermediate prostate cancer risk. ExoDx offers a urine-based test that enhances the diagnostic process for prostate cancer. Known for its ease of use, this test provides valuable insights into key molecular signatures of prostate cancer, contributing to risk assessment and treatment decision-making. It serves as an intermediary tool, allowing both PSA and MRI scans to yield more informative results. Urologist Ali Kasraeian finds it particularly beneficial in patient management, as it aids in determining whether a biopsy is warranted. This non-invasive screening option, suitable for men aged 50 and older, can be conveniently ordered and administered, utilizing advanced technology to assess the likelihood of prostate cancer, particularly for cases with a Gleason score of 7 or higher.
Biomarker testing, including ExoDx, Prolaris, Decipher, and Oncotype Dx, also plays a crucial role in guiding clinical decisions, especially for patients hesitant about undergoing biopsy procedures. By providing a quantifiable risk assessment, these tests empower patients to better understand their potential for prostate cancer, strengthening the discussions around diagnosis and treatment. Dr. Kasraeian underscores the significance of biomarkers, likening them to predictors of future biological behavior, crucial for distinguishing between indolent and aggressive forms of the disease. Notably, in cases of uncertainty following PSA velocity and MRI scan assessments, biomarker testing serves as a complementary tool, aiding urologists in refining their diagnostic approach and treatment strategies.
[Dr. Jose Silva]
…What are the options for screening? Right now, rectal exam, PSA, is there anything else you're using as a screening?
[Dr. Ali Kasraeian]
Again, the challenging discussion from that standpoint is when we see patients, or I see someone who, most of my practice is elevated PSAs, prostate cancer management, and things of that nature. By the time I see a patient, often they're coming in for a discussion of whether or not to get a biopsy, they have an elevated PSA, what do we do with that?... You have the PSA, you have % free PSA, which gives you some information.
Nowadays, we have biomarkers. You have things like the Exosome Dx, which is a great test. It's a urine-based test where if someone has a PSA where you wonder if that PSA warrants a biopsy, or if they have a PSA that's up and down, can you potentially get some more information of whether or not their PSA is associated with an intermediate or higher risk prostate? What is the risk of a Gleason 7 or higher prostate cancer? They do a urine-based test and this test can give them information or give the clinician information about that risk. Very easy to do.
[Dr. Jose Silva]
Does it have anything to do with the PSA? For example, there are some biomarkers or some screening tests that the PSA needs to be above 4 to be more sensitive or less than 10, or it's just a pure PCR test. How does it work?
[Dr. Ali Kasraeian]
This looks at vesicles. It's very interesting… Some very, very smart gentleman was looking at this for completely unrelated reasons and found there were components of RNA, messenger RNA in [the vesicles]. With the RNA, it's a blueprint of DNA. You can get samples that give information about your genetic information from that aspect.
…ExosomeDx is a urine-based test, easy to use, and it's an in-between test that for the lack of a better word, lets your PSA be smarter. It also lets your MRI scan be smarter. It's something to talk to your urologist about. If you're a urologist, it’s a tool that you can use very easily. You can even order it to be sent to your patient's home so that it uses very smart technology to see if your patient's PSA is due to a prostate cancer that's at least in 7 or higher.
Which biopsies can you avoid and which ones should you not avoid? It can complement other things. If you're someone who likes to have an MRI scan as part of your algorithm, which I do, this is a beautiful complement to it. If you are trying to have a patient that doesn't want to do a biopsy that they may or may not need it, this helps us make that decision.
If it's something where you're following a patient who has erratic PSAs that are going up and down, it helps in that. There's so many different scenarios that you can use it and it's something that's covered and it's something that's easy for patients to do.
Do you get it alone? Can you complement it with an MRI scan? If you have a low score, a cut-off point has been in the past at 15.6. If that score is lower, you have a less than 10% risk of having a Gleason 7 or higher prostate cancer. For example, if someone either does not want to do a biopsy and there's a dilemma between the urologist and the [patient], or if someone has a PSA that keeps bouncing up and down, or if it's someone who's had previous biopsies, and they've been negative, you can do an MRI scan plus a test like this.
You can get a test like this to decide whether or not to do an MRI scan. There are people with pacemakers that sometimes can't do an MRI scan.
When COVID pandemic hit, a lot of people were scared to come into the clinic. You had situations in terms of what to do, people weren't going to get lab tests. We worked with a few other centers to create a pilot of being able to send people this test into their homes where they could do these urine tests and send them into the clinic, so you can facilitate smarter screening with a biomarker that people could do at home. It really, really helped us make smarter decisions about what to do based on that.
[Dr. Jose Silva]
You were sending the patients based on if the PSA was above four, if the PSA was increasing, what were your criteria to use this product?
[Dr. Ali Kasraeian]
For me, PSA in terms of a number is variable. You can do a PSA between 2 to 10. Some other biomarkers have 4 to 10 criteria. Right now, there's a thing called an ISO PSA, which is a very intriguing PSA test. It gives you information, it gives you the PSA, it gives you the % free PSA. It's a blood test. Again, if the score is above six or so, your risk of prostate cancer is higher. Again, it's a test that gives you a cut-off point that right now you can use for a PSA 4 or higher in that 4 to 10 range.
For me, I look at your total history. If a patient comes to me with an elevated PSA, if they haven't had a recent PSA, I repeat it. If they've had a very stable PSA, it all of a sudden has gone up, I repeat it. I don't really ever act on one PSA. I look at PSA velocity. If a PSA over the past year or so has changed by a factor of 0.75, I pay mind to it. There are some studies that show that multiple PSA changes of 0.4 matter. That's something that we look at.
Then I potentially add these biomarkers as information if it makes a difference. For example, if someone has an abnormal rectal exam, if your PSA is drastically changing, and we're going to do a biopsy anyway, you take this information in stride. If doing a biomarker is not going to change our decision, then getting just another test for the sake of getting other tests may not make that much of a difference. Sometimes you have patients who absolutely and adamantly refuse to do a biopsy. Getting a biomarker, when they see that percentage risk is very high, it's amazing how it opens their eyes to that possibility. It's a very powerful thing for them to see that they may have a risk of prostate cancer. It allows us to have a different conversation when they see that, so it can be helpful.
[Dr. Jose Silva]
Yes. That patient with a Gleason 7, DRE is normal, MRI normal, maybe then that will definitely benefit from the ExosomeDx to see if he needs the biopsy or not.
[Dr. Ali Kasraeian]
That's the power of the biomarkers, although right now you really can't order biomarkers on people that have a diagnosis of prostate cancer… The first thought in our brain is that it's a really powerful use of a biomarker that supposedly can tell us the risk of a Gleason 7 versus a Gleason 6 cancer. If someone is on active surveillance and has a negative MRI scan and we can do an ExosomeDx, we can do a 4K score, we can do a biomarker designed to pick up risk of Gleason 7 cancer, we should be able to figure out a way or be able to do studies to figure out a way to use that test to help us delay future biopsies.
That's a question that I know the companies bring up quite often, but it'd be wonderful to see a test or studies to help us prove that to be able to use those to delay the biopsy or the frequency of the biopsies in between for active surveillance. I don't think right now you can use any of the biomarkers in the prostate cancer setting, unfortunately.
[Dr. Jose Silva]
Let’s say a patient that has a PSA of 12/13, maybe a 120-gram prostate, the insurance denied the MRI. You do biopsy, only a Gleason three plus Gleason six in two cores. You know that there might be something else and the ExosomeDx might be, "Hey, there is something else, let's look for it."
[Dr. Ali Kasraeian]
Absolutely. I agree with you… Are you using genomics and things of that nature in your practice? Things like Prolaris, Decipher, Oncotype, and things after diagnosis?
[Dr. Jose Silva]
I use Decipher.
[Dr. Ali Kasraeian]
These are great tests. They give us information about the potential biological activity. I tell them it tells you is a cat in a bag going to grow up to be a kitten or a ferocious tiger? It gives us that idea of the potential of these cancers later. Where the strongest value for this is-- low volume three plus four, high volume six. Is this something you watch or is this something that you treat? Could you potentially use some of these other tests, later on, to decide whether or not to continue watching or not?
[Dr. Jose Silva]
Exactly. Just like you mentioned, I used the Decipher for a patient, 5% Gleason three plus four, are you going to treat this guy fully or are you going to do an active surveillance or do something else? That's where I've been using it.
[Dr. Jose Silva]
Right now, how do you decide when to do a biopsy?
[Dr. Ali Kasraeian]
For me, the way to do a biopsy or the decision to make the biopsy, obviously talking to the patient. It sounds generic to say, but it is a very important part of that discussion. The tools we're using, the PSA, the biomarkers, the MRI scan, all of these things are wonderful tools and growing tools to help us make a personalized decision together to avoid missing a prostate cancer that could potentially impact someone's life.
…What I use to make my decisions about doing a biopsy is the trajectory of PSA change and the MRI scan. Then as a complement, if I need to, if there's a question about what that PSA is doing, if the MRI scan isn't a deciding factor, I do use the biomarkers to help make that decision as well. A lot of times that biomarker is often a helpful tool in the decisions with the patient.
I do see a lot of patients that actually come see me because they've had a lot of people talk to them about do you need a biopsy? They, themselves, do not want to get a biopsy. These tools help them see whether they need a biopsy, or we can safely rule out that they don't need a biopsy. That's how I use these tools to help me make sure I don't miss anything but also ensure that if we're not going to do a biopsy it's safe to do that.
[Dr. Jose Silva]
Exactly. At least for me, my practice for the past three years, it was during the pandemic because for some reason I couldn't do the biopsies in the office. I started doing biopsies in the OR under sedation. I started doing the MRI more often. Before I was doing the MRI after a negative biopsy to see if I missed something. Now I have incorporated and unfortunately, I'm seeing more positive cancer but I'm doing less biopsies than before.
Now the ones that I'm doing biopsy are unfortunately most likely going to have cancer, but like before most of them didn't [get a biopsy]. It's bad news for the patient that I decided to do a biopsy, but I definitely need to start incorporating biomarkers. There's still some patients that will benefit from a biomarker and I'm not using it. That's something that I'm going to have to integrate in my practice.
[Dr. Jose Silva]
In other organs, we try to do sparing of most of the organs so hopefully at some point, we'll get to the prostate being the disease standard trying to preserve most of it.
Podcast Contributors
Dr. Ali Kasraeian
Dr. Ali Kasraeian is a private practice urologic oncologist in Jacksonville, Florida.
Dr. Jose Silva
Dr. Jose Silva is a board certified urologist practicing in Central Florida.
Cite This Podcast
BackTable, LLC (Producer). (2023, March 8). Ep. 85 – New Technologies for Prostate Screening [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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